Scientists unmask body's immune cells that fight dengue

Millions get infected by dengue virus globally but a better
understanding about the immunological responses in patients during clinical
disease has been lacking. Now, in a joint study, researchers in India, Thailand
and the USA report1 "the most comprehensive analysis" of
immune blood cells in dengue patients that has important implications for
developing better vaccines.

The CD8 T cells are a class of lymphocytes (blood cells)
that are of particular interest from vaccination perspective because of their
role in eliminating virus infected targets through cytotoxic effect. In the
case of dengue, however, it has been thought that these cells, while giving
protection, might also contribute to disease.

Though the CD8 T cells' association with dengue disease had
been investigated earlier, many gaps remain. "Our studies for the first
time provide a comprehensive description of the phenotypes, functions and
molecular profiles of two major subsets of CD8 T cells," the authors say.

The researchers analysed CD8 T cells derived from peripheral
blood of 153 confirmed dengue cases – 108 from New Delhi and 45 from Bangkok – "by
using a combination of phenotypic, functional and transcriptomic
approaches."

They found that, following dengue infection, the CD8 T cells
"massively expand in numbers and show phenotypes that indicate migration
to tissues and the ability to kill virus infected cells." In fact, the
expansion of the CD8 T cells seen in dengue patients appear to be strikingly
higher than that reported in other flavivirus infections such as yellow fever, or
respiratory infections like influenza, says the report.

According to the study, results obtained in dengue patients
from India and Thailand were alike. Further, the gene expression profiles of
these cells appeared strikingly similar in dengue patients across continents,
including South America indicating that properties of these CD8 T cells are
similar in dengue patients from different geographical regions.

Most importantly the study showed that a vast majority of
CD8 T cells do not produce "cytokine interferon gamma (IFN-γ)," that
is involved in regulating the immune system's response to inflammation and
infection. This was "rather surprising," the authors say, considering
the proliferative expansion and activation of these cells and their strong
cytotoxic effect.

"Since these cells do not produce the IFN-γ, they are
likely to be protective than pathogenic during dengue," Shahid Jameel, a
virologist and CEO of Wellcome Trust/DBT India Alliance told Nature India. The finding has
"important implications for developing better dengue vaccines," he
said.

The authors conclude that an understanding of the mechanism
by which the CD8 T cells lose their capacity to produce IFN-γ can potentially
open up novel therapeutics avenues to modulate inflammation and its
pathological consequences in disease like dengue.